# One, Two, and Three Rieske Routes for Catalyzing Site-Specific Oxygenations

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $340,435

## Abstract

Abstract
Rieske oxygenases harness the reactivity of transition metals to perform powerful, efficient, and site-specific
transformations of traditionally inert bonds. These enzymes, which couple a [2Fe-2S] cluster with a non-heme
iron site, exploit molecular oxygen (O2) as a co-substrate in biosynthetic and degradative pathways. In these
reactions, the kinetic stability of O2 is overcome by the use of the non-heme iron site, which binds O2 and
promotes its cleavage via the formation of an activated oxygen intermediate. This reactive species is used to
abstract a hydrogen atom from a substrate and initiate an array of challenging transformations. Rieske
oxygenases are known to function as dioxygenases or monooxygenases, and have even been shown to catalyze
sequential monooxygenation reactions. As demonstrated in a number of biosynthetic pathways that produce
natural products with antibiotic, antifungal, anticancer, or anesthetic activities, as well as in pathways that
degrade environmental pollutants, these enzymes demonstrate exquisite control in differentiating between these
reaction types to ensure that only the intended transformation is catalyzed. Thus, these enzymes represent a
valuable source of enzymatic strategies to industrially produce pharmaceuticals and commodity chemicals, or
facilitate bioremediation efforts. However, there is a critical lack of information available about how these
enzymes are able to use a common set of metallocenters to catalyze site-specific reactions with diverse
outcomes. Therefore, in this work, we will uncover the architectural strategies that Nature uses to tune the
selectivity and catalytic repertoire of the Rieske oxygenase enzymes. This knowledge will provide predictive
power towards repurposing Rieske oxygenases to catalyze custom reactions, and will support efforts to exploit
their chemistry for a wide variety of biotechnological endeavors.

## Key facts

- **NIH application ID:** 10028367
- **Project number:** 1R35GM138271-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jennifer D Bridwell-Rabb
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,435
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028367

## Citation

> US National Institutes of Health, RePORTER application 10028367, One, Two, and Three Rieske Routes for Catalyzing Site-Specific Oxygenations (1R35GM138271-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10028367. Licensed CC0.

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